Viral Hemorrhagic Fever Diagnosis: Clinical Criteria & Laboratory Confirmation

Viral Hemorrhagic Fevers (VHFs) (Ebola, Marburg, Lassa, Crimean-Congo, Rift Valley, Dengue severe, Yellow Fever, Hantavirus) are diagnosed by combining clinical suspicion with specific laboratory testing.

Clinical Case Definition (WHO/CDC)

• Fever (≥38.3°C / 101°F) + at least two of: headache, myalgia, vomiting, diarrhea, abdominal pain, hemorrhage (petechiae, ecchymosis, epistaxis, hematemesis, melena, hematuria, vaginal), or retrosternal chest pain (Lassa).
• Epidemiologic risk within 21 days: Travel to endemic area, contact with confirmed case, lab exposure, animal contact (bushmeat, rodents).

Laboratory Diagnosis

Method	Target	Timing	Biosafety
RT-PCR (Blood/Plasma)	Viral RNA	Acute phase (days 1–10); gold standard	BSL-3/4 for Ebola/Marburg; BSL-2+ for others
Antigen Detection (RDT/ELISA)	Viral protein (NP, VP40)	Acute; rapid (RDT 15–30 min)	BSL-2/3; field-deployable for Ebola, Lassa
IgM ELISA	Acute antibody	Days 5–10 onward	BSL-2 (inactivated serum)
IgG ELISA / PRNT	Convalescent antibody	Days 10+; confirmation	BSL-2
Virus Isolation	Live virus	Definitive; research/surveillance	BSL-4 (Ebola, Marburg, CCHF)
Metagenomic NGS	Unbiased pathogen detection	Emerging; outbreak investigation	BSL-2/3

Supportive Labs (Severity & Organ Involvement)

• CBC: thrombocytopenia, leukopenia → leukocytosis, anemia.
• Coagulation: ↑PT/aPTT, ↓fibrinogen, ↑D-dimer (DIC).
• LFTs: ↑AST/ALT (hepatic necrosis), ↑bilirubin.
• Renal: ↑BUN/Cr, proteinuria.
• Electrolytes: hyponatremia, hypokalemia (GI losses).
• Lactate, troponin, CK (shock, myocarditis).

Infection Control During Workup

• Immediate isolation (single room, negative pressure if available).
• PPE: N95/PAPR, double gloves, fluid-resistant gown, face shield, boot covers.
• Dedicated equipment; minimize sharps.
• Notify public health immediately (notifiable disease).
• Sample transport: triple packaging, Category A (UN 2814).

Differential Diagnosis

• Sepsis (bacterial), severe malaria, dengue, leptospirosis, typhoid, meningococcemia, rickettsioses, TTP/HUS, DIC from other causes.